The objective of the present study was to directly compare levels of chondrocyte apoptosis produced by osteochondral injury in vivo and in vitro. Adult New Zealand White rabbits underwent 2 mm osteochondral drilling of the medial and lateral femoral condyles of a single hind limb. Animals were euthanized, and specimens were harvested at 0, 2, 4, 7, 10, and 14 days following injury. At the time of euthanasia, identical injuries were created in the femoral condyles of the contralateral hind limb. These condyles were maintained in vitro under standard tissue culture conditions until harvesting at time points corresponding to the in vivo specimens (i.e. after 0, 2, 4, 7, 10 and 14 days in culture). The extent of apoptosis in the in vivo and in vitro specimens was quantified by TUNEL analysis. The amount and distribution of TUNEL positive cells followed similar patterns in both in vivo and in vitro specimens with a maximal percentage of apoptotic chondrocytes observed on post-injury day 4. On post-injury day 4, in vivo specimens displayed a statistically significant increased overall level of apoptosis compared to in vitro specimens [in vivo = 32.5 +/- 8.6%; in vitro = 22.2 +/- 4.8%; (p = 0.03)]. These experiments suggest that the majority of programmed cell death observed after osteochondral injury can be attributed to processes intrinsic to the cartilage itself; however, additional factors present within the acutely traumatized joint also appear to potentiate chondrocyte apoptosis following injury. (C) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.